Wang, H., Boisvert, D., Kim, K.K., Kim, R. & Kim, S.H. Crystal structure of a fibrillarin homologue from Methanococcus jannaschii, a hyperthermophile, at 1.6 Å resolution. EMBO J. 19, 317-323

Department of Chemistry, University of California, Berkeley, CA 94720, USA.
The EMBO Journal (Impact Factor: 10.43). 03/2000; 19(3):317-23. DOI: 10.1093/emboj/19.3.317
Source: PubMed


Fibrillarin is a phylogenetically conserved protein essential for efficient processing of pre-rRNA through its association with a class of small nucleolar RNAs during ribosomal biogenesis. The protein is the antigen for the autoimmune disease scleroderma. Here we report the crystal structure of the fibrillarin homologue from Methanococcus jannaschii, a hyperthermophile, at 1.6 A resolution. The structure consists of two domains, with a novel fold in the N-terminal region and a methyltransferase-like domain in the C-terminal region. Mapping temperature-sensitive mutations found in yeast fibrillarin Nop1 to the Methanococcus homologue structure reveals that many of the mutations cluster in the core of the methyltransferase-like domain.

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Available from: David Boisvert, Jun 01, 2014
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    • "Proteins involved in rRNA processing are known to be among the constitutive components of active nuclee oli of somatic cells (Shaw and Brown, 2012). Since the NLBs are formed as a result of transformation of active nucleoli of preovulatory oocytes (Choinard, 1971), we decided to find out whether fibrillarin, one of the most important factors of early rRNA processing involved in the removal of the leading 5' end of the external transcribed spacer (5''ETS) and ribose methylation in rRNA (Tollervey and Kiss, 1997; Wang et al., 2000), is conserved inside the NLBs. Fibrillarin may also play a structural role in the inactive nucleoli (Verheggen et al., 2001; Barygina et al., 2010; Bartova et al., 2010). "
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    ABSTRACT: Postnatal development of mammalian oocytes is accompanied by functional and structural remodeling of the nucleolar apparatus: the final stage of this process is the formation of large objects (up to 10 μm in diameter) termed nucleolus-like bodies (NLBs) in preovulatory GV oocytes. NLB material was shown to be essential for early embryonic development, but its composition is still uncharacterized. In the present study, the protein-binding dye fluorescein-5-isothiocyanate (FITC) was used to show that proteins characterized by a high local concentration are essential NLB components in mouse GV oocytes. One of these proteins was able to be identified for the first time using a mild treatment of oocytes with proteinase K; the protein identified was fibrillarin, a factor of early pre-rRNA processing. Fibrillarin is present in the inner NLB mass of all oocytes capable of synthesizing rRNA; however, it is not colocalized with BrUTP microinjected into oocytes in order to identify transcribed ribosomal genes, in contrast to the “surface” fibrillarin. These observations imply the accumulation of nucleolar proteins not involved in ribosome biogenesis inside the NLB. All NLBs present in an individual nucleus of an NSN-type GV oocyte contain fibrillarin and are associated with active ribosomal genes. The results obtained in the present work demonstrate that proteinase K treatment of GV mouse oocytes allows for: (1) identification of “cryptic” proteins inside the densely packed NLB material and (2) the enhancement of oocyte image quality during BrUTP-based identification of rRNA synthesis sites but (3) not for the detection of active ribosomal genes in the inner mass of the NLB. The fluorescent dye FITC can be recommended for assessment of intracellular protein localization in the oocytes of all mammalian species.
    Russian Journal of Developmental Biology 05/2015; 46(3):127-136. DOI:10.1134/S1062360415030066 · 0.31 Impact Factor
    • "Depending on the organism, fibrillarin mass ranges between 34 and 38 KDa and was originally described in the nucleolus of Physarum polycephalum (Christensen et al., 1977). It is included in the superfamily of the Rossmann-fold S-adenosylmethionine (SAM) methyltransferases (MTases) (Wang et al., 2000). The characteristics of this superfamily include a conserved SAM-binding motif, the catalytic triad/tetrad [K-D-K-(H)] and seven-stranded β-sheet flanked by α-helices to form an α-β-α structure (Rakitina et al., 2011). "
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    ABSTRACT: Fibrillarin is an essential protein that is well known as a molecular marker of transcriptionally active RNA pol I. Fibrillarin methyltransferase activity is the primary known source of methylation for more than 100 methylated sites involved in the first steps of preribosomal processing and required for structural ribosome stability. High expression levels of fibrillarin have been observed in several types of cancer cells, particularly when p53 levels are reduced, because p53 is a direct negative regulator of fibrillarin transcription. Here we show fibrillarin domain conservation, structure and interacting molecules in different cellular processes as well as with several viral proteins during virus infection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Biology of the Cell 03/2015; 107(6). DOI:10.1111/boc.201400077 · 3.51 Impact Factor
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    • "The RrmJ domain of 39 protein sequences and the three out-group proteins, fibrillarin (PDB code: 1FBN) [10], [23], vaccinia VP39 (1AV6) [24] and catechol-O- methyltransferase (1VID) [25], which are structurally and functionally similar to E. coli RrmJ, were used for the construction of a phylogenetic tree. The distance matrix was calculated using the JTT model. "
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    ABSTRACT: Ribosomal RNA large subunit methyltransferase J (RrmJ), an Escherichia coli heat shock protein, is responsible for 2'-O-ribose methylation in 23S rRNA. In mammals, three close homologs of RrmJ have been identified and have been designated as FTSJ1, FTSJ2 and FTSJ3; however, little is known about these genes. In this study, we characterized the mammalian FTSJ2, which was the most related protein to RrmJ in a phylogenetic analysis that had similar amino acid sequence features and tertiary protein structures of RrmJ. FTSJ2 was first identified in this study as a nucleus encoded mitochondrial protein that preserves the heat shock protein character in mammals in which the mRNA expressions was increased in porcine lung tissues and A549 cells after heat shock treatment. In addition, a recent study in non-small cell lung cancer (NSCLC) suggested that the FTSJ2 gene is located in a novel oncogenic locus. However, our results demonstrate that the expression of FTSJ2 mRNA was decreased in the more invasive subline (CL1-5) of the lung adenocarcinoma cells (CL1) compared with the less invasive subline (CL1-0), and overexpression of FTSJ2 resulted in the inhibition of cell invasion and migration in the rhabdomyosarcoma cell (TE671). In conclusion, our findings indicate that mammalian FTSJ2 is a mitochondrial ortholog of E. coli RrmJ and conserves the heat shock protein properties. Moreover, FTSJ2 possesses suppressive effects on the invasion and migration of cancer cells.
    PLoS ONE 03/2014; 9(3):e90818. DOI:10.1371/journal.pone.0090818 · 3.23 Impact Factor
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